Evaluation of the tolerance and effects of 1-deoxynojirimycin on insulin and glucose dynamics in healthy horses and horses at risk for insulin dysregulation.

Abstract

BACKGROUND: Insulin dysregulation (ID) is common and diminishes welfare of horses. Current management relies on diet and exercise, with variable responses and limited medical options. Alpha-glucosidase inhibitors (AGIs) might provide adjunctive therapy. HYPOTHESIS/OBJECTIVES: To evaluate the tolerance and effects of Reducose®, a Morus alba leaf extract standardized to 5% 1-deoxynojirimycin (DNJ), in healthy horses and horses at risk of ID. We hypothesized DNJ would be well-tolerated and reduce insulin responses to oral sugar tests (OSTs). ANIMALS: Twenty-seven horses: 6 healthy (Phase I), 5 at risk for ID (Phase II), and 16 at risk for ID (Phase III). METHODS: Prospective, 3-phase study. Phase I assessed tolerance of escalating oral DNJ doses (0-5000 mg q12h, 7 days each). Phase II evaluated dose-dependent effects on OST response (0-5000 mg q12h, 7 days each). Phase III assessed duration of effect (0-3 h pre-OST) at 2500 and 5000 mg q12h (28 days each). Primary outcomes were peak insulin and insulin area under the curve (AUC). RESULTS: DNJ caused no adverse effects. Insulin responses decreased in a dose- and time-dependent manner. At 5000 mg q12h, peak insulin fell from 33.4 ± 15.1 μIU/mL to 18.8 ± 9.2 μIU/mL; AUC decreased by -18.6 μIU·h/mL (95% CI, -31.7 to -5.5). In Phase III, 5000 mg significantly reduced peak insulin when OST was performed 0 h (-13.1 μIU/mL, 95% CI, -18.1 to -8.2) and 1 h (-7.4 μIU/mL, 95% CI, -12.5 to -2.4) after DNJ. Insulin AUC mirrored peak insulin. CONCLUSIONS AND CLINICAL IMPORTANCE: DNJ was well-tolerated and attenuated insulin responses to OST, supporting its potential as adjunctive therapy for ID in horses.